Parkinson’s disease gets worse over many years because dopamine neurons continue to die. Researchers have discovered a drug that prevents brain deterioration in pre-clinical models with a condition similar to Parkinson’s. The drug turns on a protective gene called DJ-1 in the brain. Because the drug is already approved by the FDA for a different disease, it is available for testing. This study will test if the drug can increase DJ-1 levels in people and slow the progression of Parkinson’s disease (PD).
In the first phase of testing, researchers will recruit 12 people with recently diagnosed PD. To minimize the risk of drug interactions, patients may not be taking levodopa or Sinemet. Over a six-month period, patients will receive increasing doses of the drug phenylbutyrate, which they will take as pills. Twice a month, the patients will come to the clinic to have blood tested for DJ-1 and phenylbutyrate. Investigators expect to find a dose of phenylbutyrate that will increase the blood DJ-1 level without causing side effects. If successful, this six-month study will lead to a larger, double-blind trial to see if phenylbutyrate can stop the progression of PD in newly diagnosed patients.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If drugs that increase protective genes such as DJ-1 can stop the progression of PD, the treatment of Parkinson’s would be revolutionized. Symptoms would not get worse, and patients might never need levodopa or other treatment. In the best-case scenario, Parkinson’s symptoms could be reversed if phenylbutyrate can reverse some of the brain cell damage. Only careful clinical studies will establish whether any of these benefits will come from phenylbutyrate.
In this study, researchers will see if the drug phenylbutyrate can turn on a protective gene in the blood and the brain. Using an oral drug as a delivery mechanism for gene therapy is a completely new concept for treating Parkinson’s disease. If successful, drugs that "turn on" DJ-1 and other protective genes could transform the treatment of Parkinson’s and perhaps other conditions, such as Alzheimer’s.